A Study in Participants With Rheumatoid Arthritis on Background Methotrexate Therapy

Phase 2

Completed

Conditions: Arthritis, Rheumatoid

Interventions: Drug: LY3009104
Drug: Placebo
Drug: Methotrexate

Registration Number: NCT01185353

Lead Sponsor: Eli Lilly and Company

Brief Summary: The purpose of this trial is to evaluate the safety and efficacy of LY3009104 in participants with Rheumatoid Arthritis (RA).

Detailed Description: This study consists of the following:

* Screening period: 4 to 28-days

* Part A: a 12-week blinded, placebo controlled treatment period

* Part B: a 12-week blinded extension period

* Part C: an optional 52-week open-label extension period

* Part D: an additional optional 52-week open-label extension period

* Follow up period: 28 days

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 301

Inclusion Criteria

Must have active RA
Must regularly use methotrexate (MTX) for at least 12 weeks before your participation in this study
Must have American College of Rheumatology (ACR) functional class I, II, or III
Must have C-reactive protein (CRP) measurement > 1.2 times upper limit of normal (ULN) or Erythrocyte Sedimentation Rate (ESR) > ULN [28 millimeters/hour (mm/hr)]
Have laboratory values that in the opinion of the investigator do not pose an unacceptable risk to the participants if study drug would be administered
Must have venous access sufficient to allow blood sampling as per the protocol
Must be reliable and willing to be available for the duration of the study and are willing to follow study procedures
Must be able to read, understand, and give written informed consent approved by Lilly or its designee and the ethical review board (ERB) governing the site
Male participants: agree to use 2 forms of highly effective methods of birth control with female partners of childbearing potential during the study
If you are a woman and you could become pregnant during this study, you must talk to the study doctor about birth control. You are required to use 2 forms of highly effective methods of birth control to avoid getting pregnant during the study
If you are a post-menopausal woman, you must be at least 45 years of age and have not menstruated for the last 12 months
If you are a woman between 40 and 45 years of age, test negative for pregnancy, and have not menstruated during the last 12 months only, you must have an additional blood test
For participants receiving corticosteroids, you must be on a dose not to exceed 10 mg of prednisone daily (or equivalent) and have been on the same dosing regimen for at least 6 weeks prior to randomization
Continue to meet inclusion criteria for Parts A and B as applicable
Part D only: have completed the 52 weeks (Week 24 to Week 76) of participation in Part C of the study without permanent study drug discontinuation and have not completed the Follow-Up Visit (approximately 28 days after the last dose of study drug)

Exclusion Criteria

Must not have received any parenteral corticosteroid administered by intra-articular, intramuscular (IM), or intravenous (IV) injection within 6 weeks prior to baseline
Must not be concomitantly using non-steroidal anti-inflammatory drugs (NSAIDS), unless you are on a stable dose within the last 4 weeks
Must not have received any prior biologic disease modifying anti-rheumatic drug (DMARD) therapy [such as Tumor necrosis factor-alpha (TNFα), interleukin (IL)-1, IL-6, T-cell or B-cell target therapies)
Must not have used DMARDs other than methotrexate (MTX), hydroxychloroquine, or sulfasalazine within the last 8 weeks
Must not have used leflunomide within the last 12 weeks and have not received cholestyramine to speed up the elimination of leflunomide from your body
Must not have previously been randomized, completed or withdrawn from this study or any other study investigating LY3009104
Must not have received prior treatment with an oral JAK inhibitor
Must not have a current or recent (within the last 30 days) viral, bacterial, fungal, or parasitic infection
Must not have had a serious infection (for example, pneumonia, cellulitis, or bone or joint infections) or atypical mycobacterial infection within the last 6 months
Must not have had symptomatic herpes zoster or herpes simplex infection within the last 90 days or have a history of disseminated/complicated herpes zoster
Must not have evidence of human immunodeficiency virus (HIV) and/or positive human HIV antibodies
Must not have evidence of hepatitis C virus (HCV) or active hepatitis B
Must not have evidence or suspicion of active or latent tuberculosis (TB)
Must not have another serious disorder or illness
Must not be exposed to a live vaccine within the last 12 weeks
Must not have donated more than 500 milliliters (mL) of blood within the last month
Must not have had surgery on a joint that is to be assessed in the study within the last 2 months, or will require such during the study
Must not be currently enrolled in, or discontinued within the last 30 days from a clinical trial involving an investigational drug or device or off-label use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study
Presence of significant uncontrolled cerebro-cardiovascular [for example (eg), myocardial infarction (MI), unstable angina (UA), unstable arterial hypertension, severe heart failure or cerebrovascular accident], respiratory, hepatic, renal, gastrointestinal (GI), endocrine, hematologic or neuropsychiatric disorders, or abnormal laboratory values that in the opinion of the investigator pose an unacceptable risk to the participant if study drug would be administered

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1 mg LY3009104 once daily	LY3009104	Administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
8 mg LY3009104 once daily	Methotrexate	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Placebo once daily	Placebo	Placebo administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 once daily	LY3009104	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
4 mg LY3009104 once daily	LY3009104	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
8 mg LY3009104 once daily	LY3009104	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 twice daily	LY3009104	(Not utilized in Part A) After 12 weeks treatment with 1 mg LY3009104 once daily or Placebo once daily in Part A, administered orally twice daily for 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
1 mg LY3009104 once daily	Methotrexate	Administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 once daily	Methotrexate	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
4 mg LY3009104 once daily	Methotrexate	Administered orally once daily for 24 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
Placebo once daily	Methotrexate	Placebo administered orally once daily for initial 12 weeks followed by randomization to either 4 mg LY3009104 once daily or 2 mg LY3009104 twice daily for an additional 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.
2 mg LY3009104 twice daily	Methotrexate	(Not utilized in Part A) After 12 weeks treatment with 1 mg LY3009104 once daily or Placebo once daily in Part A, administered orally twice daily for 12 weeks. After 24 weeks of treatment participants will be eligible to participate in an open-label extension period (Part C). Part C: 4 mg or 8 mg administered orally once daily for 52 additional weeks. After 76 weeks of treatment participants will be eligible to participate in an additional open-label extension period (Part D). Part D: 4 mg administered orally once daily for 52 additional weeks.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants in the 4 mg and 8 mg Dose Groups Who Achieved an American College of Rheumatology 20 (ACR20) Responder Index Response Baseline Through Week 12	Baseline through Week 12	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in rheumatoid arthritis (RA). An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved an ACR70 Response Baseline Through Weeks 76 and 128	Baseline through Weeks 76 and 128	ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.
Mean Change From Baseline to Weeks 76 and 128 in DAS28-CRP	Baseline, Weeks 76 and 128	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using visual analog scale (VAS) (patient's global VAS). DAS28-CRP=0.56\square root (sqrt)(TJC28)+0.28\sqrt(SJC28)+0.36\natural log(CRP+1)+0.014\patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity and remission is DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Percentage of Responders According to European League Against Rheumatism Responder Index Based on 28-joint Count (EULAR28) Baseline Through Weeks 12 and 24	Baseline through Weeks 12 and 24	EULAR28 categorizes clinical response based upon improvement since baseline in DAS modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: TJC28, SJC28, CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 12 and 24	Baseline through Weeks 12 and 24	Disease Activity Score (DAS) modified to include 28-joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP \[milligrams per liter (mg/L)\], and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 12 - Model Based Dose Response	Baseline through Week 12	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
Percentage of Participants Who Achieved an ACR20 Responder Index Response Baseline Through Week 24	Baseline through Weeks 2, 4, 8, 12, 16, 20, 24	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants treated) \* 100.
Percentage of Participants Who Achieved an ACR20 Response Baseline Through Weeks 76 and 128	Baseline through Weeks 76 and 128	ACR20 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR20 Responder is a participant who had ≥20% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥20% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR20 response = (number of ACR20 responders) / (number of participants analyzed) \* 100.
Percentage of Participants Who Achieved an ACR 50 Responder Index Response Baseline Through Week 24	Baseline through Weeks 2, 4, 8, 12, 16, 20, 24	ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.
Population PK: Area Under the Concentration Curve Versus Time at a Dosing Interval at Steady State (AUCtau,ss) of LY3009104	Baseline through 24 weeks
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Weeks 76 and 128	Baseline through Weeks 76 and 128	ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100.
Mean Change From Baseline to Weeks 12 and 24 in Disease Activity Score (DAS) Based on the 28 Diarthrodial Joint Count and CRP Level (DAS28-CRP)	Baseline, Weeks 12 and 24	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count-28 (TJC28), swollen joint count-28 (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). DAS28-CRP=0.56\square root (sqrt)(TJC28)+0.28\sqrt(SJC28)+0.36\natural log(CRP+1)+0.014\patient's global VAS+0.96. Scores ranged from 1.0-9.4, where lower scores indicated less disease activity, and remission was DAS28-CRP \<2.6. A decrease in DAS28-CRP indicated an improvement in participant's condition.
Percentage of Responders According to EULAR28 Baseline Through Weeks 76 and 128	Baseline, Weeks 76 and 128	EULAR28 categorizes clinical response based upon improvement since baseline in Disease Activity Score modified to include the 28-joint count (DAS28) and post-baseline DAS28. DAS28 consists of a composite score of the following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP, and Patient's Global Assessment of their Disease Activity (patient's global VAS). DAS28 scores range from 1.0-9.4. EULAR28 categories include: No Response (improvement in DAS28 of ≤0.6 units or post-baseline DAS28 score \>5.1 with improvement by ≤1.2 units), Moderate Response (post-baseline DAS28 ≤5.1 with improvement by \>0.6 units but ≤1.2 units or post-baseline DAS28 score \>3.2 with improvement by \>1.2 units), and Good Response (post-baseline DAS28 score ≤3.2 with improvement by \>1.2 units).
Percentage of Participants Meeting Low Disease Activity and Remission Based on the 28 Diarthrodial Joint Count (DAS28) Baseline Through Weeks 76 and 128	Baseline through Weeks 76 and 128	Disease Activity Score (DAS) modified to include 28 joint count (DAS28) consisted of composite score of following variables: tender joint count (TJC28), swollen joint count (SJC28), CRP (mg/L), and Patient's Global Assessment of Disease Activity using VAS (patient's global VAS). Scores ranged from 1.0-9.4, where lower scores indicated less disease activity. DAS28 scores ≤3.2 are considered as low disease activity, and scores \<2.6 are considered as remission. Participants who discontinue before analysis time points are treated as non-responders.
Mean Change From Baseline Through Week 12 in Duration (Minutes) of Morning Stiffness	Baseline, Weeks 4, 8, 12	The Investigator asked participants about the duration of their morning stiffness (in minutes) in and around the joints and recorded the duration. The Investigator asked the participants about duration of morning stiffness on the day prior to the study visit to capture actual symptoms. If morning stiffness duration was longer than 12 hours (720 minutes), it was truncated to 720 minutes for statistical presentations and analyses.
Mean Change From Baseline Through Week 12 in the ENSEMBLE Minimum Data Set 1.0	Baseline, 12 weeks
Percentage of Participants Who Achieved an ACR70 Responder Index Response Baseline Through Week 24	Baseline through Weeks 2, 4, 8, 12, 16, 20, 24	ACR70 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR70 Responder is a participant who had ≥70% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥70% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time points are treated as non-responders. Percentage of participants achieving ACR70 response = (number of ACR70 responders) / (number of participants analyzed) \* 100.
Mean Change From Baseline to Weeks 12 and 24 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain	Baseline, Weeks 12 and 24	Physician's and Patient's Assessments of Disease Activity (DA) assessed using a visual analog scale (VAS) that ranged from 0 to 100 millimeters (mm), where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis was also assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).
Mean Change From Baseline to Weeks 76 and 128 in Physician's Global Assessment of Disease Activity, Patient's Global Assessment of Disease Activity and Patient's Assessment of Pain	Baseline, Weeks 76 and 128	Physician's and Patient's assessments of DA assessed using a VAS that ranged from 0 to 100 mm, where 0 indicated no arthritis activity and 100 indicated extremely active arthritis. Patient's assessment of pain due to arthritis assessed using a VAS that ranged from 0 (no pain) to 100 mm (worst possible pain).
Percentage of Participants Who Achieved an ACR50 Response Baseline Through Week 12 - Model Based Dose Response	Baseline through Week 12	ACR50 Responder Index is a composite of clinical, laboratory, and functional measures in RA. An ACR50 Responder is a participant who had ≥50% improvement from baseline in both 68 tender and 66 swollen joint counts and ≥50% improvement in at least 3 of 5 criteria: Patient's and Physician's Global Assessment of Disease Activity, HAQ-DI (assessment of participant's physical function), pain due to RA, and hsCRP. Participants who discontinue before analysis time point are treated as non-responders. Percentage of participants achieving ACR50 response = (number of ACR50 responders) / (number of participants analyzed) \* 100. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
ACR Percent Improvement (ACR-N)	Baseline through Week 12	ACR-N is a continuous measure of clinical, laboratory, and functional outcomes in RA that characterizes percentage (%) of improvement in disease activity from baseline based on ACR core set. This index was calculated as minimum of a) % of improvement in TJC, b) % of improvement in SJC, and c) third highest percentage of improvement of remaining 5 ACR core criteria: If ≥3 components of the 5 ACR core criteria were missing, then c) was set to missing; if any of 3 components a), b), or c) were missing, then ACR-N was set to missing. Percentage of improvement was truncated to a range of -100 to 100 to minimize impact of outliers (greater scores indicate greater % improvement) and negative scores indicate a decline. Data presented are model-based Bayesian posterior mean response rates with 95% credible interval.
Mean Change From Baseline to Weeks 12 and 24 in Tender and Swollen Joint Counts (TJC and SJC)	Baseline, Weeks 12 and 24	TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
Mean Change From Baseline to Weeks 76 and 128 in TJC and SJC	Baseline, Weeks 76 and 128	TJC is the number of tender and painful joints determined for each participant by examination of 68 joints. Joints were assessed by pressure and joint manipulation on physical examination. Participants were asked for pain sensations on these manipulations and watched for spontaneous pain reactions. Any positive response on pressure, movement, or both was translated into a single tender-versus-nontender dichotomy. SJC is the number of swollen joints determined for each participant by examination of 66 joints. Joints were classified as either swollen or not swollen. Swelling was defined as palpable fluctuating synovitis of the joint.
Mean Change From Baseline to Weeks 12 and 24 in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score	Baseline, Weeks 12 and 24	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Mean Change From Baseline to Weeks 76 and 128 in HAQ-DI Score	Baseline, Weeks 76 and 128	The HAQ-DI questionnaire assesses the participant's self-perception on the degree of difficulty \[0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)\] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
Mean Change From Baseline to Weeks 12 and 24 in High-Sensitivity C-Reactive Protein (hsCRP)	Baseline, Weeks 12 and 24	hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Mean Change From Baseline to Weeks 76 and 128 in hsCRP	Baseline, Weeks 76 and 128	hsCRP is a laboratory analyte that is an indicator of inflammation. Decreases in hsCRP represent reductions in inflammation.
Mean Change From Baseline to Weeks 12 and 24 in Erythrocyte Sedimentation Rate (ESR)	Baseline, Weeks 12 and 24	ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Mean Change From Baseline to Weeks 76 and 128 in ESR	Baseline, Weeks 76 and 128	ESR is a laboratory analyte that is an indicator of inflammation. Decreases represent reductions in inflammation.
Population Pharmacokinetics (PK): Maximum Concentration at Steady State of Dosing (Cmax,ss) of LY3009104	Baseline through 24 weeks
Mean Change From Baseline to Week 12 in Medical Outcomes Study 36-Item Short Form (SF-36) Health Survey Physical Component Summary (PCS) and Mental Component Summary (MCS) Scores	Baseline, Week 12	The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains (physical functioning, bodily pain, role limitations due to physical problems and also emotional problems, general health, mental health, social functioning and vitality) and 2 component scores (PCS and MCS). The PCS score consisted of physical functioning, bodily pain, role-physical, and general health scales. The MCS score consisted of social functioning, vitality, mental health, and role-emotional scales. Both PCS and MCS range from 0-100 with higher scores indicating better health or functioning.
Mean Change From Baseline to Week 12 in Brief Pain Inventory Modified Short Form (BPI-sf Modified) Worst-Pain-in-the Past-24-hours Item Score	Baseline, Week 12	The BPI-sf modified is a self-administered questionnaire developed for the rapid assessment of pain. The BPI-sf modified provides information on the intensity of pain (the sensory dimension) as well as the degree to which pain interferes with function (the reactive dimension). The questionnaire asks questions about pain relief, pain quality, and the participant's perception of the cause of pain. The BPI-sf modified uses a numeric rating scale from 0 ("No pain") to 10 ("Pain as bad as you can imagine"). Since pain can be quite variable over a day, the BPI-sf modified asked participants to rate their pain at the time of responding to the questionnaire (right now), and also at its worst, least and average over the last 24 hours.
Mean Change From Baseline to Week 12 in Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F) Score	Baseline, Week 12	The FACIT-F Scale is a brief 13-item, symptom-specific questionnaire that specifically assesses the participant self-reported severity of fatigue and its impact upon daily activities and functioning. The FACIT-F uses a numeric rating scale of 0 ("Not at all") to 4 ("Very much") for each item to assess fatigue and its impact in the past 7 days. Total scores range from 0 to 52, with higher scores indicating less fatigue.

Trial Locations

Locations (1): For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
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Vinnytsya, Ukraine